Studying dynamic intermolecular interactions of human histone deacetylase 8: activity, regulation and recruitment

• Applicant: Professor Dr. Nicolas Werbeck
• Subject Area: Structural Biology ; Biochemistry
• Term: from 2014 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 251894764

The acetylation of lysine side-chains is an important post-translational modification involved in the regulation of central cellular events ranging from transcription to protein degradation. Histone deacetylases (HDACs) play a crucial role in these processes by removing the acetyl-group from lysines of histones and non-histone-proteins and they are implicated in the development and therapy of diseases such as cutaneous T-cell lymphoma. Despite a wealth of in-vivo and in-vitro data and numerous crystal structures very little is known about the molecular mechanism of their regulation and their interaction with cellular binding partners. Here, we propose to map and characterise molecular interactions of the class I human histone deacetylase 8 by using nuclear magnetic resonance spectroscopy as well as biochemical and computational approaches. We aim to study the interactions involved in substrate binding, phosphorylation and phosphorylation-dependent recruitment of HDAC8 and provide molecular models for the regulation of deacetylase activity. The results will contribute to our understanding of the role HDACs play in a tightly interconnected cellular network and may provide possible avenues for rational interventions of these processes in the context of HDAC associated diseases.

• DFG Programme: Research Fellowships
• International Connection: United Kingdom
• Host: Dr. D. Flemming Hansen